Differences in invasion between human smooth muscle cells from umbilical vein, saphenous vein and internal mammary artery: relation to the expression of the plasminogen activation system

Abstract

Smooth muscle cells can express a range of phenotypes. Smooth muscle cells from intimal thickenings are phenotypically different from media smooth muscle cells. Migration and proliferation are important processes involved in the development of intimal t hickening. Several studies have demonstrated the role of the plasminogen activation system in the migration and proliferation of smooth muscle cells. In this study we determined the proliferation and invasion capacity of smooth muscle cells (SMC) that we re isolated from three different types of vessels; saphenous vein (SV), internal mammary artery (IMA), and umbilical vein (UV). Whereas we found no differences in proliferation, we show that there are clear differences in the expression of t-PA, u-PA, an d PAI-1 and subsequent differences in plasminogen activator activity between the smooth muscle cell types. Whereas u-PA activity was low in all three cell types studied, t-PA activity was lowest in UV-SMC (0.25IU/10⁶cells), and higher in SV-SMC (0.8IU/10⁶cells) and IMA-SMC (1.2IU/10⁶cells). These findings could in part explain the differences we found in the invasion capacity of the smooth muscle cell types in an in vitro matrix invasion assay. Whereas the invasion of SV-SMC could be inhibited by an inhibitor of plasmin (aprotinin), the invasion of UV-SMC could not. Furthermore, the invasion of UV-SMC could be stimulated by active t-PA or u-PA, whereas the invasion of SV-SMC could not. The results for IMA-SMC were, however, more variable. These findings toget her suggest that phenotypically different smooth muscle cells exist between different vessel types, and may explain some of the differences in the ability of vessels to develop intimal thickening.